SnET2 for the treatment of vascular disease: dose/response study in New Zealand white (NZW) rabbits

Tin ethyl etiopurpurin, SnET2, is presently undergoing clinical trials for the treatment of cutaneous cancers and AIDS related Kaposi's sarcoma. Extensive pre-clinical work has been performed investigating the uptake, localization, and retention of SnET2 in catheter induced atheromatous plaques in New Zealand White (NZW) rabbits and juvenile female swine. The ultimate goal is to employ SnET2 for the prevention of intimal hyperplasia following various forms of angioplasty, thus enabling the prevention of a significant cause of restenosis. To that end, a dose/response study was undertaken to investigate the effect of varying total light dose (200, 100, and 50 J/cm2) and light dose rate (637, 318, 159 mW/cm2) during SnET2-Photodynamic Therapy, SnET2-PDT, of catheter induced plaque in a NZW rabbit iliac artery model. The SnET2 dose was held constant at 1.0 mg/kg b.w. and light was delivered intraluminally via a guidewire compatible light diffusing balloon catheter. The greatest light dose of those tested without inducing thermal damage was found to be 318 mW/cm2 while the total light dose of 50 J/cm2 produced PDT effect which was limited to the neo-intima. A relatively substantial total light dose of 200 J/cm2 was shown to produce a transmural PDT effect. This study demonstrated that the depth of PDT effect can be modulated by varying the total light dose.

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